Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Feb 27, 2018; 10(2): 308-318
Published online Feb 27, 2018. doi: 10.4254/wjh.v10.i2.308
Survival outcomes of liver transplantation for hepatocellular carcinoma in patients with normal, high and very high preoperative alpha-fetoprotein levels
Wong Hoi She, Albert Chi Yan Chan, Tan To Cheung, Chung Mau Lo, Kenneth Siu Ho Chok
Wong Hoi She, Department of Surgery, University of Hong Kong, Hong Kong, China
Albert Chi Yan Chan, Tan To Cheung, Chung Mau Lo, Kenneth Siu Ho Chok, Department of Surgery and State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong, China
Author contributions: She WH contributed to study conception and design, data acquisition, analysis, interpretation and manuscript drafting; Chan ACY, Cheung TT and Lo CM contributed to critical revision of the manuscript; Chok KSH contributed to study conception and design, drafting and revision of the manuscript; all authors approved the submitted version of the paper.
Institutional review board statement: Institutional review board approval was not required for this retrospective study since treatments given to patients were not influenced by the study and the clinical data used in the study are anonymous.
Informed consent statement: Patients’ consent to this retrospective study was not required since treatments given to patients were not influenced by the study and no individual patients would be identified as the clinical data used in the study are anonymous.
Conflict-of-interest statement: None of the authors has any conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Kenneth Siu Ho Chok, FRCS (Ed), Associate Professor, Department of Surgery, University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China.
Telephone: +852-22553025 Fax: +852-28165284
Received: November 23, 2017
Peer-review started: November 24, 2017
First decision: December 12, 2017
Revised: December 18, 2017
Accepted: February 5, 2018
Article in press: February 5, 2018
Published online: February 27, 2018
Research background

Liver transplantation is the best treatment option for hepatocellular carcinoma. However, only patients’ tumor criteria should fit the current adopted selection criteria. Most of the criteria are morphological descriptions, including size and number, with the recently added alpha-fetoprotein in some of the updated criteria.

Research motivation

We hoped to identify the cutoff value of alpha-fetoprotein in predicting disease recurrence and overall survival. Apart from using size and number as the selection criteria for liver transplantation, the additional use of alpha-fetoprotein might be able to give practical prediction of disease recurrence.

Research objectives

The objective of this study is to investigate the impact of alpha-fetoprotein on the long-term recurrence rate and overall survival of recipients of liver transplantation for hepatocellular carcinoma.

Research methods

Data of adult patients who received liver transplantation for hepatocellular carcinoma at our hospital from January 2000 to December 2013 were reviewed. Data of included patients were analyzed. We defined the different levels of alpha-fetoprotein as normal (< 10 ng/mL), high (≥ 10 to < 400 ng/mL) and very high (≥ 400 ng/mL). The patients were divided into these 3 groups accordingly. Group comparison was then made.

Research results

Alpha-fetoprotein level was normal in 83 patients, high in 131 patients, and very high in 36 patients. The commonest etiology was hepatitis-B-related cirrhosis. The Model for End-stage Liver Disease scores in these groups were similar (median, 13 vs 13 vs 12; P = 0.745). Patients with normal alpha-fetoprotein level had longer time to operation (median, 94 vs 31 vs 35 d; P = 0.001). The groups were similar in hospital mortality (P = 0.626) and postoperative complication (P = 0.702). Pathology of explants showed that the 3 groups had similar numbers of tumor nodules, but patients with very high alpha-fetoprotein level had bigger tumors (P = 0.003). This group also had a bigger proportion of patients who were beyond Milan criteria (P = 0.010). Poor differentiation and vascular permeation were commoner in this group (P = 0.017 and P = 0.003 respectively). It also had poorer 5-year overall survival (P = 0.029) and disease-free survival (P = 0.007). Receiver operating characteristic area under the curve for alpha-fetoprotein in predicting tumor recurrence was 0.685. The selected cut-off value was 54 ng/mL (C-index 0.685; 95%CI: 0.592-0.779; sensitivity 0.595; specificity 0.687). On discriminative analysis, alpha-fetoprotein value of 105 ng/mL was shown to affect the overall survival of the patients.

Research conclusions

This study showed that patients with high preoperative alpha-fetoprotein levels had poorer post-transplant survival. An alpha-fetoprotein level of 54 ng/mL was associated with disease recurrence, and 105 ng/mL was found to be the cutoff value for overall survival difference. These findings would be useful when considering liver transplantation for patients with a high alpha-fetoprotein level. Currently, there is no definite cutoff value of alpha-fetoprotein for ideal oncological outcomes in hepatocellular carcinoma. With the above alpha-fetoprotein values, superior long-term disease-free and overall survival will be achievable if liver transplantation is offered to patients with a lower preoperative alpha-fetoprotein level. The additional use of alpha-fetoprotein will allow better prediction of the long-term survival outcome, and hence affect the future practice in selection of patients for liver transplantation.

Research perspectives

Selection of patients for liver transplantation should not be based on morphological criteria alone. Other biomarkers such as alpha-fetoprotein should be added to the criteria currently used.